Northampton County EMS also confirmed a firefighter was transported for treatment after becoming overheated while at the scene near the 180 exit.
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The North Carolina State Department of Transportation said in a statement I-95 South is closed near mile marker 178, due to the crash.
The roadway is expected to re-open by 5 p.m.
Motorists are advised to use the following detour:
I-95 South Traffic: Take Exit 4 in Virginia; Turn left onto VA-629 East to US-301; Turn right onto US-301 South and proceed approximately 12 miles to NC-46; Turn right on NC-46 West to re-access I-95 South.
Trooper T.J. Blount of the state Highway Patrol said the crash occurred after a tractor-trailer collided with a van. The van caught fire and burned.
The tractor-trailer then collided with a small passenger vehicle and another tractor-trailer was knocked off the road into a ditch.
Troopers were still investigating as of this report.